This invention relates to drug delivery compositions and devices and more particularly to polymeric compositions and devices for the delivery of bioactive agents to the periodontal pocket.
Periodontal disease often arises from the presence of pathogenic bacteria in the gingival pocket surrounding teeth. Disease arising from the pathogenic bacteria is treated with anti-microbial agents that are delivered in a variety of irrigation, systemic delivery and controlled delivery. Mouth rinses are relatively poor at reaching the site of the disease activity but good in providing adequate drug concentration. The duration of therapy is poor while patient compliance is fair. Subgingival irrigation is good in reaching the site of disease activity and providing adequate drug concentration but provides poor duration of therapy and only fair patient compliance. Systemic delivery is good at reaching the site of the disease activity but provides only fair drug concentration, duration of therapy and patient compliance. In contrast, controlled drug delivery would be characterized as good in each of the categories.
Current delivery systems include a collagen-based Periochip(trademark) which is easy to insert into the gingival pocket but provides a sub-optimal release profile, is difficult to place when wet and has limited efficacy. Atridox(trademark) injectable polymer is easily placed but has limited efficacy, is difficult to retrieve and generates systemic effects. Actisite(trademark) EVAC (LVAX) fiber is efficacious but is difficult to place.
It is therefore an object of the present invention to develop a drug delivery system that will provide improved encapsulation efficiency and release characteristics of anti-microbials in a polymeric delivery system. The system will allow for easy manipulation of drug lipophilicity, protect the drug from premature degradation and be easily adapted to various delivery device configurations.
The drug delivery composition of the invention includes a polymeric material, a complexing agent, and a bioactive agent complexed with the complexing agent. The polymeric material, the complexing agent, and the bioactive agent are formed into a delivery matrix or chip.
In a preferred embodiment, the complexing agent has a hydrophobic core and a hydrophilic exterior. A suitable complexing agent is xcex2-cyclodextrin which may be methyl- xcex2-cyclodextrin or hydroxy-propyl xcex2-cyclodextrin or any derivatives thereof. The bioactive agent may be a hydrophobic anti-microbial such as chlorhexidine or chlorhexidine digluconate. Other suitable anti-microbials include tetracycline, tobramycin and gentamicin. A suitable polymeric material PLGA co-polymer. Other polymers ate suitable such as photoreactive polymers. The drug delivery composition may also include water-soluble additives such as sugars, salts or poly (ethylene oxide) and derivatives and co-polymers thereof. Poly (ethylene glycol) is also suitable.
A preferred embodiment of the drug delivery composition of the invention includes PLGA co-polymer, cyclodextrin, and chlorhexidine or chlorhexidine digluconate complexed. with the cyclodextrin. The composition is compressed to form a delivery matrix such as a chip.
The drug delivery composition of the invention allows for the delivery of hydrophobic drugs, controls burst effect and increases encapsulation efficiency. The complexing agent protects the drug and alters solubility and lipophilicity of the drug. The use of PLGA allows a steady state release profile.